The surface porteins of animal cells play an important role in cell structure, receptor function, transport, and other interactions between a cell and its environment. Many of these proteins are differentiation antigens, restricted to a certain set of cells, and act on the specific functions of that cell. Studies of these proteins are important to understanding (a) the function of cells, (b) the mechanisms of differentiation of normal and cancer cells, and 9c) the role of cell receptors in the control of cell function and the response to drugs. The goal of this research is to identify, purify and characterize cell surface proteins of mouse embryo 3T3 cells. This will include studies of the chemical and physical properties, synthesis and metabolism, expression in vivo in different mouse cells and tissues, genetic control of expression, and biological functions of the proteins. The methodology is to prepare monoclonal antibodies that identify specific cell surface proteins by immunoprecipitation and to use these antibodies for protein purification by antibody affinity chromatography. We have previously used this approach to identify 8 cell surface proteins and purify the first 5 of these. There remain a very large number of other cell surface proteins that are yet unidentified. The monoclonal antibodies, purified protein and polyclonal antiserum can then be used for characterization of the proteins. Proteins that act as differentiation antigens will be identified; for example, three of the previously identified proteins are expressed in vivo as differentiation antigens of mouse macrophage and other phagocytic cells. The physical properties of the proteins as they relate to cell differentiation will be studied. Monoclonal antibodies that identify polymorphic antigens will be selected for genetic mapping of the gene(s) that control protein expression. Studies of biologic function will emphasize (a) a search for mutant mice, and (b) analysis of a previously observed association between a 90,000 Mr cell surface protein and a 70,000 cytoskeleton-associated protein.